OVATION-2: A randomized phase I/II study evaluating the safety and efficacy of IMNN-001 (IL-12 gene therapy) with neo/adjuvant chemotherapy in patients newly-diagnosed with advanced epithelial ovarian cancer.

OBJECTIVE: OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC). METHODS: IMNN-001 is an immunotherapeutic nanoparticle comprising a DNA plasmid encoding the IL-12 gene encased in a lipopolymer. High-grade EOC patients were randomized 1:1 to carboplatin/paclitaxel IV every 21 days for 3 cycles, before and after interval debulking surgery (IDS) or to intraperitoneal (IP) IMNN-001, given weekly concurrently with chemotherapy for 8 weeks before and 9 weeks after IDS. RESULTS: 54 and 58 patients with predominantly Stage IIIC/IV EOC were evaluated in the control and experimental arm, respectively. Primary endpoints were safety and PFS. Overall, the experimental arm was well tolerated with gastrointestinal and cytopenias as the most common TEAEs with no CRS or elevated risk of immune events. PFS was 14.9 months (mo) for the experimental arm vs 11.9 mo; HR 0.79 (95 % CI: 0.51-1.23). Secondary endpoints included OS (46.0 mo for experimental arm vs 33.0 mo; HR 0.69 (CI: 0.40-1.19)) and surgical response R0 rate (64.6 % experimental arm vs 52.1 %). For patients who received PARPi maintenance, PFS was 33.8 mo vs 22.1 mo; HR 0.80 (CI: 0.31-2.12) and OS was NE vs 37.1 mo with a HR of 0.38 (CI: 0.13-1.06) both favoring the experimental arm. CONCLUSION: The addition of IMNN-001 to N/ACT shows a promising numerical 13-mo benefit on survival with an acceptable safety profile in patients with newly-diagnosed advanced EOC

Molecular Correlates of Long-Term Response to Bevacizumab in Glioblastoma.

Purpose: The use of bevacizumab in glioblastoma has been associated with increased progression-free survival and improvement in symptoms and quality of life. There are no clinical indicators on how to choose patients who would benefit the most from this agent. We aim to describe molecular markers in patients with glioblastoma who may benefit from treatment. Methods: We analyzed glioblastoma tumor samples that underwent comprehensive molecular profiling analysis at Caris Life Sciences. Results: The data set consisted of 3,106 glioblastoma tumor samples, of which 571 were from patients treated with bevacizumab. The majority were males (65%) and older than 60 years. Median survival was 17.5 months in patients receiving bevacizumab. In patients who were treated with bevacizumab for ≥1 year, median survival was 33.8 months, compared with 15 months in those treated for ≤6 months. Patients who received bevacizumab for ≥1 year had higher prevalence of LRIG3 (9% v 1%), CDK4 (22% v 8%), and DDIT3 amplification (14% v 4%), SETD2 mutations (10% v 3%), and MGMT methylation (66% v 32%). EGFR amplification was more frequent in patients who received bevacizumab for ≤6 months (46% v 20%). Multivariate analysis showed that CDK4 amplification was associated with longer time on bevacizumab, and EGFR amplification with shorter time after correcting for age, sex, and other molecular alterations. Conclusion: CDK4 amplification is a potential genetic biomarker to identify patients who may derive prolonged benefit from bevacizumab

Comparative Analysis of Injury and Illness Rates Among Team USA Athletes at the Tokyo 2020 Summer Olympic and Paralympic Games.

BACKGROUND: Previous research has reported higher rates of both injury and illness among Paralympic athletes compared with Olympic athletes during the Winter Olympic and Paralympic Games, but no studies have directly compared injury and illness incidence between Olympic and Paralympic athletes competing in a Summer Games. PURPOSE: To compare injury and illness rates between Olympic and Paralympic Team USA athletes competing in the Tokyo 2020 Olympic and Paralympic Games. STUDY DESIGN: Descriptive epidemiology study. METHODS: All injuries and illnesses that occurred among the Team USA athletes competing in the Tokyo 2020 Summer Olympic or Paralympic Games were documented. A total of 701 Team USA athletes (53.6% female) competed in the Tokyo 2020 Summer Olympic Games, across 34 different sports. For the Tokyo 2020 Summer Paralympic Games, a total of 245 athletes (51.6% female) competed across 20 sports. Incidence rates (IRs) per 1000 athlete-days were calculated according to sex, sport, anatomic location, and illness type. IR ratios (IRRs) were calculated to compare IRs between male and female athletes and between Olympic and Paralympic athletes. RESULTS: Overall, there were no differences in injury incidence (IRR, 1.18; 95% CI, 0.84-1.68) or illness incidence (IRR, 0.68; 95% CI, 0.41-1.15) between Olympic and Paralympic athletes. Male Paralympic athletes were less likely to sustain an illness compared with female Paralympic athletes (IRR, 0.35; 95% CI, 0.11-0.90). CONCLUSION: There were no differences in injury or illness rates between Olympic and Paralympic Team USA athletes competing at the Tokyo 2020 Summer Games, contrary to previous comparisons among winter sport athletes. These results challenge the prevailing notion that Summer Paralympic athletes are at greater injury and illness risk, suggesting that factors beyond Olympic or Paralympic Games participation influence health concerns

Impact of Delay of Treatment With Disease-Modifying Antirheumatic Drugs in Psoriatic Arthritis: The CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Objective: Our objective was to describe characteristics and compare clinical and patient-reported outcomes (PROs) for disease-modifying antirheumatic drug (DMARD)-naive patients with psoriatic arthritis (PsA) who initiate DMARD therapy early versus late. Methods: Patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry were classified by reported time between diagnosis and DMARD initiation. Early and late initiators were patients whose first DMARD treatment occurred ≤1 year or \u3e1 year, respectively, following PsA diagnosis. Change in disease activity and PRO measures from initiation to the six-month follow-up was calculated for each group; mean change for each continuous outcome and proportion achieving binary outcomes were reported for early and late initiators. Associations of early versus late DMARD initiation with disease activity and PROs at six months were calculated using adjusted linear and Poisson regressions. Results: The mean patient age was 53 years, more than half of patients were female, and 90% of patients were White. Mean time from diagnosis to DMARD initiation was 0.2 years in early initiators (n = 229, 79%) and 8.6 years in late initiators (n = 62, 21%). In adjusted analyses, achievement of minimal disease activity (adjusted risk ratio 2.01, 95% confidence interval [CI] 1.03-4.40) and mean change in Clinical Disease Activity Index (β -3.4, 95% CI -6.2 to -0.49) were statistically different between early and late initiators. Conclusion: Among patients from the PsA registry, those who had both early and late initiation of DMARD therapy experienced improvements throughout all disease activity and PROs across six months of treatment. Minimal disease activity, a key treatment target, was more likely observed in early initiators, highlighting the value of early identification and treatment. Delay of Treatment With Disease-Modifying Antirheumatic Drugs in Psoriatic Arthritis: The CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry

Estimation of the value-based price of a blood test for Alzheimer\u27s disease pathology in primary and specialty care in the U.S.

BACKGROUND: Blood tests for the pathology of Alzheimer\u27s disease (AD) are emerging as alternative to amyloid PET scans and analysis of cerebrospinal fluid. (CSF). However, their economic value, which depends on test accuracy as well as effect on clinical decision-making, remains unclear. METHODS: We use a Markov model to estimate the value-based price of a blood test with sensitivity of 88 % and specificity of 89 %, if labeled for triage and confirmation of the AD pathology in primary and specialty care. The value-based price was defined as price of the test, at which overall diagnostic cost per true positive case of early-stage AD would equate that under standard of care (identification in primary care and referral to specialty care based on the results of a brief cognitive test). Assumptions for the effect of test use on clinical decisions came from a structured expert consultation process. RESULTS: If used in primary care, the value-based price would be $290 for a triage and$1150 for a confirmatory test, respectively, as use of PET or CSF testing would decline by 47 % and 86 %, respectively. If used in specialty care, i.e., after confirmation of early-stage cognitive impairment, the overall number of blood tests would decline. Consequently, the value-based price would increase to $450 for a triage test and$1950 for a confirmatory test. CONCLUSIONS: The results project substantial cost savings from implementing a blood test for AD pathology within the diagnostic pathway based on modeling results, which future research should confirm with actual data

Treatment adherence patterns for patients with atherosclerotic cardiovascular disease: Patient and provider perspectives.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality, affecting more than 500 million individuals globally. National guidelines recommend lipid-lowering therapies (LLTs) as first line agents for both primary and secondary prevention of ASCVD. However, under-prescribing of pharmacologic LLTs and sub-optimal medication adherence remain common problems. AIM: This mixed-methods study aimed to identify patient and prescriber factors influencing adherence to LLTs. METHODS: Patients with an ASCVD diagnosis and treatment plan that included LLT were sampled from a large community health system serving seven states. A stratified random sample of 2500 patients was surveyed by mail, capturing barriers and facilitators to medication adherence using an adapted version of the Adherence Starts with Knowledge-12 (ASK-12) scale, achieving a 16.2 % response rate (406 patients). Twenty-three semi-structured interviews were conducted with a sample of patient survey respondents to further explore drivers of non-adherence. Eligible prescribers with experience treating patients with ASCVD were surveyed by email, resulting in a 3.3 % response rate (122 respondents). Survey data were analyzed descriptively and using regression models; interview data were analyzed thematically. RESULTS: While cohort patients were identified as having an ASCVD diagnosis and taking a LLT from their medical chart, only 16.8 % of respondents reported having an ASCVD diagnosis and 84.2 % reported taking LLTs. Patients taking medication reported a higher average number of health condition diagnoses compared to those not taking a medication (2.63 and 1.50, respectively). Of those taking medication, 55.7 % were identified as adherent. Non-adherent patients were more likely to report poor healthcare experiences and social determinants of health needs. Multivariable regression analysis revealed that patients were more likely to be adherent when they felt their healthcare provider always spent enough time with them and treated them with respect. Interview findings further emphasized the importance of healthcare experiences, convenience, and belief the treatment works as important factors to adherence. In contrast, prescribers perceived higher non-adherence rates, citing forgetfulness and medication inconvenience as the main barriers. However, only 10.0 % of responding prescribers reported using a tool to assess patients\u27 medication adherence and only 42.6 % reported asking patients about changes to their medication regimens. CONCLUSION: A substantial proportion of patients reported adherence to their medications, with adherence being associated with positive healthcare experiences, self-reported health conditions, perceived effectiveness of the medication, and social determinants of health needs. Prescribers perceived relatively low adherence among their patients, however only a small percent reported using tools to assess medication adherence. Comprehensive assessment tools and open communication could optimize patient care and enhance medication adherence and treatment outcomes

Outcomes of Mothers and Infants Affected by COVID-19.

The long-term effects of the novel coronavirus disease 2019 (COVID-19) infection during pregnancy are poorly characterized in mothers and their infants. The aim of this study was to assess the physical, mental, and emotional well-being of mothers and infants in the first year postpartum who were exposed to and/or diagnosed with COVID-19 infection.This direct-to-participant cohort study recruited 96 mother-infant pairs delivering at Pediatrix Medical Group sites, where mothers tested positive for COVID-19 during their pregnancy or birth hospitalization and/or infants tested positive for COVID-19 prior to hospital discharge. Main outcome measures included scored responses to surveys administered at 6 and 12 months postpartum and infant health status from newborn admission through the first year after birth.Mothers with COVID-19 infection during pregnancy often reported persistent physical, mental, and emotional stress affecting both themselves and their infants. Scores assessing infant temperament were higher than reported in prior literature. Infants were relatively healthy throughout their first year after birth.The experience of COVID-19 infection during pregnancy may create a unique set of circumstances that affects the well-being of infants and their mothers separately as well as the child-caregiver relationship. Early life events have the potential to generate lasting consequences; therefore, it is important to identify these issues to maximize support and intervene if indicated. · Experiencing COVID-19 in pregnancy is unique.. · Possible effects on temperament, and relationships.. · This impact may persist for at least 1 year postpartum.

June 2025: Region 10 Emerging Special Pathogen Treatment Center (RESPTC) at Providence Sacred Heart Medical Center & Children’s Hospital

REGION 10 SPECIAL PATHOGENS NEWSLETTERhttps://digitalcommons.providence.org/special_pathogens_newsletters/1008/thumbnail.jp